Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury

Abstract. Acute kidney injury (AKI) is a severe complication of sepsis with a high mortality and morbidity. Pterostilbene (Pte) has been suggested to confer anti-apoptotic and anti-inflammatory effects. In the current study, the effects of Pte on AKI were evaluated in septic mice. Cecal ligation and puncture surgery was performed to induce sepsis. The results suggested that Pte administration significantly decreased the levels of serum urea nitrogen and creatinine, and improved the survival rate of septic mice. Additionally, the renal injury induced by sepsis was attenuated by pterostilbene treatment. Notably, pterostilbene reduced Bcl-2-associated X protein expression, and levels of interleukin-1β and tumor necrosis factor-α, and upregulated B-cell lymphoma 2 expression. The results indicate that pterostilbene may serve as a potential therapeutic candidate for the treatment of AKI induced by sepsis.

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“…Sepsis-induced AKI accounts for nearly 50% of cases of AKI in the ICU (14). Moreover, AKI is the leading cause of death in the ICU (15).…”

Section: Discussionmentioning

confidence: 99%

Pterostilbene attenuates acute kidney injury in septic mice

et al. 2018

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“…In systemic sepsis, bacterial products termed PAMPs (pathogen-associated molecular pattern molecules; eg, endotoxin) are described to bind to pattern recognition receptors on leukocytes and most other cell types (the classic receptors being Toll-like receptors [TLRs]), resulting in activation of multiple cell types. 27,28 Circulating activated leukocytes reportedly extravasate into the tissue of target organs after being exposed to chemokines and adhesion molecules (eg, ICAM-1, E-selectin) on the surface of the activated endothelium (and chemokines in the tissue). 29 The release of proinflammatory cytokines from these leukocytes, in combination with activated tissue macrophages, are discussed as a major event leading to organ/tissue dysfunction and injury that occurs in sepsis in multiple species and equine laminitis.…”

Section: Discussionmentioning

confidence: 99%

Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically‐Relevant Timepoint in the Oligofructose Laminitis Model

Dern

Eps

Wittum

et al. 2017

Veterinary Internal Medicne

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BackgroundAlthough continuous digital hypothermia (CDH) protects lamellae from injury in the oligofructose (OF) model of sepsis‐related laminitis (SRL), conflicting results exist from these studies regarding effects of CDH on lamellar inflammatory events.Hypothesis/ObjectivesTo determine the effect of CDH on lamellar inflammatory events in normal and OF‐treated horses when instituted at a clinically relevant time point (onset of clinical signs of sepsis in this model).AnimalsStandardbred geldings (n = 15) aged 3–11 years were used.MethodsIn a randomized, controlled discovery study, animals were administered either OF (OF group, n = 8) or water (CON group, n = 8) by nasogastric tube and CDH was initiated in one forelimb (ICE) 12 hours later. Lamellar tissue samples were collected 24 hours after initiation of CDH (ICE and ambient [AMB] forelimbs). Lamellar mRNA concentrations of inflammatory mediators and lamellar leukocyte numbers were assessed using qPCR and immunohistochemistry, respectively; values from four sample groups (CON AMB, OF AMB, CON ICE, and OF ICE) were analyzed using mixed model linear regression.ResultsAlthough lamellar mRNA concentrations of multiple inflammatory mediators (IL‐1β, IL‐6, CXCL1, MCP2, COX‐2) were increased after OF administration (OF AMB group versus CON AMB; P < 0.05), only 2 inflammatory mediators (IL‐6 and COX‐2) and lamellar leukocyte numbers were decreased with CDH (OF ICE versus OF AMB; P < 0.05).Conclusions and Clinical ImportanceContinuous digital hypothermia initiated at a time point similar to that commonly used clinically (clinical onset of sepsis) resulted in a more focused inhibition of inflammatory signaling.

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“…Toll‐like receptor 4 as one of the major outer membrane components of Gram‐negative bacteria is a major player in the LPS‐induced AKI inflammatory response . The TLR4 signalling pathway is activated at the initiation of LPS‐induced inflammatory response, then its downstream pathway NF‐κB is activated, and NF‐κB activation induces the release of inflammatory factors . When the inflammatory factors in the cells are released, the inactive NF‐κB in the cytoplasm is rapidly transferred to the nucleus to regulate the inflammatory cytokines .…”

Section: Discussionmentioning

confidence: 99%

“…[4] The TLR4 signalling pathway is activated at the initiation of LPS-induced inflammatory response, then its downstream pathway NF-jB is activated, and NF-jB activation induces the release of inflammatory factors. [14] When the inflammatory factors in the cells are released, the inactive NF-jB in the cytoplasm is rapidly transferred to the nucleus to regulate the inflammatory cytokines. [15,16] Therefore, the TLR4 signalling pathway can be considered an effective therapeutic target for AKI induced by LPS.…”

Section: Discussionmentioning

confidence: 99%

S-nitrosoglutathione protects lipopolysaccharide-induced acute kidney injury by inhibiting toll-like receptor 4–nuclear factor-κB signal pathway

Fan

Zhao²,

Zhu

2019

Journal of Pharmacy and Pharmacology

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Objectives To investigate the therapeutic effects and mechanisms of S‐nitrosoglutathione (SNG) on acute kidney injury (AKI) induced by lipopolysaccharide (LPS). Methods We established an AKI model by intraperitoneal administration of LPS in mice and LPS‐induced human kidney (HK‐2) cells in vitro. We obtained the kidney tissues from mice for histopathological examination, examined inflammatory cytokines by enzyme‐linked immunosorbent assay and measured the expression levels of toll‐like receptor 4–nuclear factor‐κB (TLR4–NF‐κB) signal pathway‐related proteins by Western blotting. Key findings Pretreatment of SNG effectively improved the kidney function, reduced the pathological damage score of kidney in mice and decreased the expression levels of IL‐1β, IL‐6 and TNF‐α in a dose‐dependent manner in vivo and in vitro. Furthermore, pretreatment of SNG also repressed TLR4, phosphorylated NF‐κB IκBα, IKKβ and p65 expression levels in HK‐2 cells induced by LPS. Conclusions S‐nitrosoglutathione attenuates the severity of LPS‐induced AKI by inhibiting the TLR4–NF‐κB signalling pathway and may act as a protective agent for septic AKI.

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Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury

Cited by 69 publications

References 138 publications

Pterostilbene attenuates acute kidney injury in septic mice

Pterostilbene attenuates acute kidney injury in septic mice

Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically‐Relevant Timepoint in the Oligofructose Laminitis Model

S-nitrosoglutathione protects lipopolysaccharide-induced acute kidney injury by inhibiting toll-like receptor 4–nuclear factor-κB signal pathway

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